STimulation to Activate RespIration (STARI)

A Clinical Study Evaluating Temporary Transvenous Diaphragm Neurostimulation in Mechanically Ventilated Patients With Acute Hypoxemic Respiratory Failure

Multi-center, randomized, controlled, open-label Phase 2 feasibility trial. Subjects on mechanical ventilation (MV) for acute hypoxemic respiratory failure (AHRF) with lung injury (including subjects who meet criteria for acute respiratory distress syndrome (ARDS)) will be randomized 2:1 to diaphragm neurostimulation-assisted ventilation (DNAV) using the AeroNova System plus lung-protective ventilation (Treatment) vs. lung-protective ventilation alone (Control).

Study Overview

• Status: Recruiting
• Conditions: Mechanically Ventilated ICU Patients; ARDS (Moderate or Severe); AHRF
• Intervention / Treatment: Device: Phrenic Nerve Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Megan O'Toole; Phone Number: (484) 350-4530; Email: motoole@lungpacer.com
• Study Contact Backup: Name: STARI Study; Phone Number: (484) 350-4530; Email: STARIstudy@lungpacer.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • University Health Network (UHN)
      • Principal Investigator: Ewan Goligher, MD
• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California San Diego
      • Principal Investigator: Kenneth Chen, MD
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Recruiting
      • Louisiana State University Health Sciences
      • Principal Investigator: Jonathan Eaton, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Principal Investigator: Eduardo Mireles-Cabodevila, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19122
      • Recruiting
      • Temple University
      • Principal Investigator: Gerard Criner, MD
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Recruiting
      • Prisma Health
      • Principal Investigator: Matthew Varner, DO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, 18 years or older, and
2. Able to provide informed consent or have a legally authorized representative (LAR) / Substitute Decision Maker (SDM) who can provide consent, and
3. Have acute onset of new respiratory symptoms or dysfunction within the 2 weeks before onset of need for respiratory support, and

4. Have arterial hypoxemia defined by one of:

   • PaO2:FiO2 ratio ≤300 mm Hg on PEEP ≥5 cm H2O, or
   • In the absence of an available arterial blood gas, SpO2 ≤97% on FiO2 ≥0.5 and PEEP ≥5 cm H2O with reliable SpO2 trace for the 2 hours immediately preceding eligibility assessment (this correlates to an upper limit of SpO2:FiO2 ratio of 316%) or
   • Are receiving pulmonary vasodilators for acute hypoxemia, or
   • Are being ventilated in the prone position for acute hypoxemia, and
5. Have been mechanically ventilated for AHRF in the ICU for <96 hours at the time of enrolment, and
6. Are expected to require invasive mechanical ventilation ≥48 hours after enrollment in the opinion of the treating clinician

Exclusion Criteria:

1. Hypoxemia is primarily attributable to acute exacerbation of chronic obstructive pulmonary disease, status asthmaticus, cardiogenic pulmonary edema, or pulmonary embolism.
2. Underlying chronic parenchymal lung disease that may make recovery/extubation a challenge (e.g., COPD, pulmonary fibrosis).
3. Broncho-pleural fistula at the time of eligibility assessment.
4. Require extracorporeal membrane oxygenation.
5. Pre-existing neurological, neuromuscular or muscular disorder or known phrenic nerve injury that could affect the respiratory muscles.
6. BMI >70 kg/m2.
7. Contraindications to left internal jugular vein or left subclavian vein catheterization (e.g., infection at the access site, known central venous stenosis, septic thrombophlebitis, left internal jugular ECMO cannula in situ, poor target vessels).
8. Patient expected to transition to fully palliative care within 72 hours of enrollment.
9. Chronic severe liver disease (e.g., Child-Pugh Score ≥10)
10. Treating clinician deems enrollment not clinically appropriate.
11. Currently enrolled in any other study of an investigational drug or device, which may affect the outcomes of the current study.
12. Any electrical device (implanted or external) that may be prone to interaction with or interference from the AeroNova System, including neurological pacing/stimulator devices and cardiac pacemakers and defibrillators.
13. Known or suspected to be pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Treatment group subjects will have the Catheter placed percutaneously into the left jugular vein or left subclavian vein. Mapping will identify the electrodes that stimulate the phrenic nerves and enable diaphragm contraction using the AeroNova Console. The stimulation level will be titrated to target a level of diaphragm activation equivalent to resting quiet breathing by adjusting the stimulation frequency and amplitude. Subjects will receive continuous stimulation plus standard of care lung-protective ventilation.	Device: Phrenic Nerve Stimulation; During controlled MV when patients are not breathing, continuous diaphragm neurostimulation-assisted ventilation (DNAV) will be delivered in synchrony with each ventilator-delivered breath.; Other Names: Diaphragm neurostimulation-assisted ventilation (DNAV)
No Intervention: Control; Standard of Care - Lung-protective ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Successful device insertion, mapping, and initiation of stimulation within 18 hours of meeting readiness-to-stimulate criteria	Within 18 hours of meeting readiness to stimulate criteria
Stimulation delivered on >50% of ventilator-triggered breaths (ascertained from continuous recordings stored in the Console)	30 days
Rehabilitation sessions delivered at least once per day on >50% of days when the patient was breathing in assisted (patient-triggered) mechanical ventilation	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Unanticipated serious adverse device events (USADE) and incidence of device- or procedure-related SAEs in the Treatment group	30 days

Collaborators and Investigators

• Sponsor: Lungpacer Medical Inc.
• Investigators: Principal Investigator: Ewan Goligher, MD, PhD, FRCPC, Toronto General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 14, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Follicular
• Other Study ID Numbers: P-600; 75A0123C00021 (Other Grant/Funding Number: Biomedical Advanced Research and Development Authority (BARDA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No